Tex14, a Plk1-Regulated Protein, Is Required for Kinetochore-Microtubule Attachment and Regulation of the Spindle Assembly Checkpoint

• Published in: Molecular cell Vol. 45; no. 5; pp. 680 - 695
• Main Authors: Mondal, Gourish, Ohashi, Akihiro, Yang, Lin, Rowley, Matthew, Couch, Fergus J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.03.2012
• Subjects: Binding Sites; CDC2 Protein Kinase - metabolism; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Chromosome Segregation; HEK293 Cells; HeLa Cells; Humans; kinetochores; Kinetochores - metabolism; Kinetochores - ultrastructure; M Phase Cell Cycle Checkpoints; metaphase; microtubules; Microtubules - metabolism; Microtubules - ultrastructure; mitosis; Phosphorylation; Polo-Like Kinase 1; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Transcription Factors - analysis; Transcription Factors - genetics; Transcription Factors - physiology
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2012.01.013

Proper assembly of kinetochores (KTs) during mitosis is required for bipolar attachment of spindle microtubules (MTs) and the accumulation of spindle assembly checkpoint (SAC) components. Here we show that testis-expressed protein 14 (Tex14), which has been implicated in midbody function, is recruited to KTs by Plk1 in a Cdk1-dependent manner during early mitosis. Exclusion of Tex14 from kinetochores results in an inability to efficiently localize outer KT components, impaired KT-MT attachment, chromosome congression defects, and whole-chromosome instability. In addition, we demonstrate that phosphorylation of Tex14 by Plk1 during metaphase promotes APCCdc20-mediated Tex14 degradation. Inhibition of this phosphorylation event causes retention of Tex14 at KTs and results in delayed metaphase-to-anaphase transition and chromosome segregation defects. Our findings identify Tex14 as an important mediator of KT structure and function and the fidelity of chromosome separation. ► Tex14 is recruited to kinetochores by Plk1 ► Outer kinetochore markers fail to localize to kinetochores in the absence of Tex14 ► Tex14 is required for kinetochore-microtubule attachment and accurate chromosome congression ► Plk1-dependent degradation of Tex14 regulates the metaphase-to-anaphase transition